A monoclonal antibody (mAb), RE2, directly kill activated lymphocytes without participation of complement through a novel pathway of call death. The present study was carried out to clarify the mechanism of and participating molecules of this novel type of cell death and to establish specific immunosuppressive method using this mAb. Using expression cloning method, we cloned the genes coding for the molecules reactive with the mAb. MHC class I molecules (KィイD1kィエD1 and KィイD1bィエD1) were turned out to be target molecules of RE2 mAb. However, antibody specific to KィイD1kィエD1, 11-4.1, did not induce cell death in the activated lymphocytes. Therefore, we think that the unknown molecule(s) associated with KィイD1kィエD1 or KィイD1bィエD1 is responsible for this novel type of cell death.Alloantigen-specific tolerance was successfully induced by fractionated irradiation together with injection of alloantigen. We think the combined treatment of animals with fractionated irradiation and RE2-administration may provide a stable method of tolerance induction.